The hosts are currently sitting top of the League One table, while the U's head into the midweek round fixtures in 16th position.
Match preview
Portsmouth have established a six-point lead at the League One summit after winning four and drawing one of their last five matches.
Pompey began that fine run of form with consecutive away wins over Fleetwood Town and Port Vale, before they were held to a 2-2 draw by Oxford United at the Kassam Stadium.
After returning to winning ways against Northampton Town, Pompey recorded another victory in Saturday's away meeting with basement side Carlisle United.
Paddy Lane scored just after the hour mark to guide John Mousinho's side to a narrow 1-0 win, representing their third victory in their last four away matches.
Portsmouth have now recorded 15 clean sheets in their 32 league matches, and they will try to produce another defensive display in Tuesday's contest as they go in search of their 10 home win of the League One season.
Cambridge, meanwhile, will have to pick themselves up after their four-game unbeaten run was brought to an end by Cheltenham Town on Saturday.
A second-half strike from Cheltenham's Matty Taylor proved enough to condemn Cambridge to their first defeat since losing to Leyton Orient on New Year's Day.
Having won nine, drawn eight and lost 12 of their 29 matches, the U's are fighting to secure their League One status with four points separating them from the drop zone.
Although Cambridge have won just two of their 13 away games in the third tier this season, they do have the chance to claim consecutive away wins for the first time since April 2022 after beating Shrewsbury Town on their most recent road trip.
They may have failed to win any of their last three meetings with Portsmouth, but the U's managed to take a point off the league leaders in October's goalless draw at Abbey Stadium.
Portsmouth League One form:
L
W
W
D
W
W
Cambridge United League One form:
W
D
D
W
D
L
Team News
Portsmouth are expected to be without the services of Zach Swanson, Tom McIntyre, Regan Poole, Joe Morrell, Terry Devlin, Tino Anjorin and Alex Robertson.
Abu Kamara could be presented with a starting berth after coming off the bench to provide an assist for Lane's winner against Carlisle.
Colby Bishop will continue to lead the line for the hosts, having scored 15 goals in 30 league appearances this season.
As for the visitors, James Brophy could return to the starting lineup after dropping down to the bench for the last two matches.
Having scored three goals in five appearances, January signing Lyle Taylor is expected to retain his place up front.
Gillingham loanee Macauley Bonne will continue to provide Neil Harris with a useful option off the bench after making a couple of substitute appearances following his arrival in the winter transfer window.
Portsmouth possible starting lineup:
Norris; Rafferty, Raggett, Shaughnessy, Ogilvie; Lowery, Pack; Kamara, Lang, Lane; Bishop
Cambridge United possible starting lineup:
Stevens; L. Bennett, R. Bennett, Morrison, Andrew; Digby, Cousins; Brophy, Kachunga, Kaikai; Taylor